Mechanisms for Vascular Dysfunction and Exercise Tolerance in CF

NCT02690064 | Active Not Recruiting DMC

• 1 other identifier: CF-AOX
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

Cystic fibrosis has many health consequences. A reduction in the ability to perform exercise in patients with CF is related to greater death rates, steeper decline in lung function, and more frequent lung infections. However, the physiological mechanisms for this reduced exercise capacity are unknown. The investigators recently published the first evidence of systemic vascular dysfunction in patients with CF. Therefore, it is reasonable to suspect that the blood vessels are involved with exercise intolerance in CF. This study will look at how and if oxidative stress contributes to both artery dysfunction and exercise intolerance in CF.

Conditions

Cystic Fibrosis

Keywords

Endothelial Function; Maximal Exercise Capacity; Flow Mediated Dilation; Antioxidant; FEV1

Outcome Measures

Primary Outcomes (4)

• Acute Change in Flow mediated dilation

  Flow-Mediated Dilation will be determined at baseline and 2 hours following acute antioxidant treatment

  Change from baseline (2 hours)

• Chronic Change in Flow mediated dilation

  Flow-Mediated Dilation will be determined at baseline, week 4, week 8 and week 12.

  Baseline, week 4, week 8, and week 12

• Acute Change in exercise capacity (VO2 peak)

  Subjects will perform a baseline maximal exercise capacity test and on a separate visit perform a maximal exercise capacity test 2 hours following acute antioxidant treatment

  Baseline and 2 hours following acute antioxidant treatment

• Chronic Change in exercise capacity (VO2 peak)

  Subjects will perform a maximal exercise capacity test at baseline, week 4, week 8, and week 12.

  Baseline, week 4, week 8, and week 12

Study Arms (2)

Acute Antioxidant Treatment

EXPERIMENTAL

Following an overnight fast, blood samples, flow-mediated dilation, lung function, and exercise capacity (VO2 peak) (post only) will be performed at baseline and 2 hours following either a single dose oral 1) antioxidant cocktail (1000 mg Vitamin C, 600 IU vitamin E, 600 mg Alpha Lipoic Acid) 2) Resveratrol (1500 mg) 3) Mitoquinol (10 mg) or placebo on two days separated by at least 72 hours.

Dietary Supplement: Acute Antioxidant; Other: Placebo

Chronic Antioxidant Treatment

EXPERIMENTAL

Following the completion of Arm 1, blood samples, flow-mediated dilation, lung function, and exercise capacity (VO2 peak) will be performed, only in patients with CF, at baseline, 4 weeks, 8 weeks, and 12 weeks following one of the following: 1) an anti-oxidant cocktail (vitamin C 1000 mg, vitamin E 400 IU, and alpha lipoic acid 600 mg) taken once a day, 2) 1500 mg Resveratrol once a day or 3) 10 mg Mitoquinol once a day.

Dietary Supplement: Chronic Antioxidant

Interventions

Acute Antioxidant DIETARY_SUPPLEMENT

Flow-Mediated Dilation will be determined at baseline and 2 hours following acute antioxidant treatment

Also known as: Vitamin C, Vitamin E, Alpha Lipoic Acid, Resveratrol, Mitoquinol (MitoQ)

Acute Antioxidant Treatment

Chronic Antioxidant DIETARY_SUPPLEMENT

Flow-Mediated Dilation will be determined at baseline, week 4, week 8, and week 12.

Also known as: Vitamin C, Vitamin E, Alpha Lipoic Acid, Resveratrol, Mitoquinol (MitoQ)

Chronic Antioxidant Treatment

Placebo OTHER

Flow-Mediated Dilation will be determined at baseline and 2 hours following acute antioxidant treatment

Acute Antioxidant Treatment

Eligibility Criteria

• Age: 7 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of CF and healthy controls
• Men and women (\> 18 yrs. old)
• Boys and girls (7-17 yrs. old)
• FEV1 percent predicted \> 30%
• Patients with or without CF related diabetes
• Resting oxygen saturation (room air) \>90%
• Traditional CF-treatment medications
• Ability to perform reliable/reproducible PFTs
• Clinically stable for 2 weeks (no exacerbations or need for antibiotic treatment within 2 weeks of testing or major change in medical status)
• Pancreatic sufficient and pancreatic insufficient patients

You may not qualify if:

• Children 6 yrs. old and younger
• FEV1 percent predicted \< 30%
• Resting oxygen saturation (room air) \< 90%
• Clinical diagnosis of heart disease, PAH
• Febrile illness within two weeks of visit
• Currently smoking, pregnant, or nursing
• Individuals on vaso-active medications (i.e. nitrates, beta blockers, ACE inhibitors, etc.)
• Patients with B. cepacia (only \~3% of our CF center patient population)
• Treatment for pulmonary exacerbation within 4 weeks of a study visit

Sponsors & Collaborators

• Augusta University: lead

Study Sites (1)

Georgia Prevention Institute

Augusta, Georgia, 30912, United States

Location

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

Ascorbic Acid; Vitamin E; Thioctic Acid; Resveratrol; mitoquinol

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Intervention Hierarchy (Ancestors)

Sugar Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Hydroxy Acids; Carbohydrates; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Thiophenes; Sulfur Compounds; Coenzymes; Enzymes and Coenzymes; Fatty Acids; Lipids; Stilbestrols; Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polyphenols; Phenols

Study Officials

• Ryan Harris, Ph.D.

  Augusta University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 19, 2016
• First Posted: February 24, 2016
• Study Start: April 1, 2015
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): January 1, 2027
• Last Updated: January 28, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share

Locations

US (1)